US1925472A - Processes for converting coca alka - Google Patents
Processes for converting coca alka Download PDFInfo
- Publication number
- US1925472A US1925472A US1925472DA US1925472A US 1925472 A US1925472 A US 1925472A US 1925472D A US1925472D A US 1925472DA US 1925472 A US1925472 A US 1925472A
- Authority
- US
- United States
- Prior art keywords
- ecgonine
- alkaloids
- coca
- converting
- alka
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 241000735552 Erythroxylum Species 0.000 title description 12
- 235000008957 cocaer Nutrition 0.000 title description 12
- 238000000034 method Methods 0.000 title description 10
- 229930013930 alkaloids Natural products 0.000 description 38
- 239000003513 alkali Substances 0.000 description 28
- PHMBVCPLDPDESM-FKSUSPILSA-N Ecgonine Chemical class C1[C@H](O)[C@H](C(O)=O)[C@H]2CC[C@@H]1N2C PHMBVCPLDPDESM-FKSUSPILSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 14
- PHMBVCPLDPDESM-GHNGIAPOSA-N Pseudoecgonine Chemical class C1[C@H](O)[C@@H](C(O)=O)C2CCC1N2C PHMBVCPLDPDESM-GHNGIAPOSA-N 0.000 description 12
- PHMBVCPLDPDESM-YWIQKCBGSA-N Ecgonine Natural products C1[C@H](O)[C@@H](C(O)=O)[C@H]2CC[C@@H]1N2C PHMBVCPLDPDESM-YWIQKCBGSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 229930002959 ecgonine Natural products 0.000 description 10
- 230000002035 prolonged Effects 0.000 description 10
- 238000006136 alcoholysis reaction Methods 0.000 description 8
- ZPUCINDJVBIVPJ-BARDWOONSA-N cocaine Natural products O([C@@H]1C[C@H]2CC[C@H](N2C)[C@@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-BARDWOONSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- QIQNNBXHAYSQRY-UYXSQOIJSA-N ecgonine methyl ester Chemical compound C1[C@H](O)[C@H](C(=O)OC)[C@H]2CC[C@@H]1N2C QIQNNBXHAYSQRY-UYXSQOIJSA-N 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 235000011121 sodium hydroxide Nutrition 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 230000003197 catalytic Effects 0.000 description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 4
- 229960003920 cocaine Drugs 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000000875 corresponding Effects 0.000 description 4
- YBNSZTYCRZTRRX-JLVJUDLZSA-N methyl (1R,5S)-4-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-3-carboxylate Chemical compound C1([C@@H]2CC[C@@H](N2C)CC1C(=O)OC)OC(=O)C1=CC=CC=C1 YBNSZTYCRZTRRX-JLVJUDLZSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 101700028200 COCA Proteins 0.000 description 2
- 210000004940 Nucleus Anatomy 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000005844 autocatalytic reaction Methods 0.000 description 2
- 238000006480 benzoylation reaction Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000003472 neutralizing Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000001184 potassium carbonate Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000750 progressive Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000005429 turbidity Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
- C07D451/12—Oxygen atoms acylated by aromatic or heteroaromatic carboxylic acids, e.g. cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
- C07D451/10—Oxygen atoms acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine
Definitions
- My invention has for its object the direct conversion into ecgonine methylic ester of the greater part of the amorphous alkaloids (so-called secondary alkaloids) which are found with cocaine in the coca leaves, by treatment with alkalies in a solution of methylic alcohol or any other alcohol capable of dissolving the alkalies.
- secondary alkaloids amorphous alkaloids
- Another characteristic of my invention consists in the use of very small quantities of alkali which are sufficient to cause said conversion, the latter thus consisting in a catalytic alcoholisis of the alkaloids.
- alkaloids separate intomethylic esters of the acid radicals connected to the ocgonine nucleus and in ordinary levo-methylecgonine.
- methylated ecgonine is very sensitive to the action of alkalies of which a small quantity of methylicsolution is suificient to cause its progressive conversion into dextro-methylatedecgonine (or d. I' methyl-ecgonine). There is in this case a secondary catalytic isomeration effect upon the levoester formed in the first place in the division due to the action of the alkalies. This is a general property of the alkyl-ecgonines.
- Oxides and alcoholates of alkali and alkaline earth metals, ammonia, certain amines and quaternary ammonium hydrates may be used as catalysts. Any alcohol capable of dissolving the catalyst may also be used as solvent of the alkaloids in the place of methylic alcohol.
- the corresponding cocaines may be produced Without difiiculty by benzoylating according to the usual methods the ecgonine or pseudo-ecgonine esters.
- Ammonia is gradually added to the acid solution with agitation as long as a reaction takes place and a turbidity is present due to the separation of unattached amorphous alkaloids. Thereafter the unattached alkaloids thus separated are removed'by agitationwith benzene in 9 which they dissolve. Said alkaloids are separated from the solvent by distillation and may be treated in a new process. 1
- the alkaline solution is then saturated with potassium carbonate which causes separation of the methylated ecgonine which is also recovered by stirring with benzene.
- the solvent is distilled ofi in vacuum.
- the methylecgonine thus produced may be directly submitted to benzoylation or purified by conversion in hydrochloride.
- the mode of operation is the same as above described but at the end of the first three days of contact there will again be added 20 grs. of NaOH per kg. of alkaloids which are left to act during a week, at the end of that time the operation is begun to recover the methylpseudoecgonine into alkylated derivatives of ecgonine and dextro pseudo-ecgonine which consists in treating the alkaloids dissolved in an alcohol with small quantities of a compound having a strongly alkaline reaction, acting catalytically in homogeneous medium at room temperature and for a prolonged period to produce alcoholysis of said alkaloids and subsequent isomerization of the alkyl-ecgonine first produced. 7
- a process for converting the alkaloids of coca into dextrorotary pseudo ecgonine esters which comprises subjecting these alkaloids to alcoholysis, and subsequently catalytically forming the isomers of the alkyl-ecgonines first formed by contacting the same with an alkaline catalyst at room temperature and for a prolonged period.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Catalysts (AREA)
Description
Ratenied Sept. 5, 1933 PROCESSES FOR CONVERTING COCA ALKA- LO'IDS INTO ALKYLATED DERIVATIVES OF ECGONINE AND PSEUDO-ECGONINE Auguste Tirard, St.-uen, France, assignor .to
Societe Anonyme St.-Ouen, France Etabliss ements Roques',
No Drawing. Application July 10, 1930, Serial No. 467,143, and in France June 25, 1930 4 Claims.
It has long since been made known by Liebermann and Giesel, German Patent No. 47,602 and U. S. Patent No. 450,887 of April 21, 1891 that through the action of alkalies the amorphous coca 5 alkaloids may be divided in two parts viz in ecgonine and organic acids.
On the other hand Boehringer & Soehne, Ger man Patent #55,338-Eichorn and Marquardt, Berichte XXIII (1890) page 468 have disclosed that said alkaloids are converted in dextroecgonine or pseudo-ecgonine by the prolonged action of concentrated alkalies.
My invention has for its object the direct conversion into ecgonine methylic ester of the greater part of the amorphous alkaloids (so-called secondary alkaloids) which are found with cocaine in the coca leaves, by treatment with alkalies in a solution of methylic alcohol or any other alcohol capable of dissolving the alkalies.
Another characteristic of my invention consists in the use of very small quantities of alkali which are sufficient to cause said conversion, the latter thus consisting in a catalytic alcoholisis of the alkaloids. These alkaloids separate intomethylic esters of the acid radicals connected to the ocgonine nucleus and in ordinary levo-methylecgonine.
I have now found moreover that unlike the ecgonine which necessitates a prolonged heating with a large excess of alkali in order to be converted in deXtro-ecgonine or pseudo-ecgonine,
methylated ecgonine is very sensitive to the action of alkalies of which a small quantity of methylicsolution is suificient to cause its progressive conversion into dextro-methylatedecgonine (or d. I' methyl-ecgonine). There is in this case a secondary catalytic isomeration effect upon the levoester formed in the first place in the division due to the action of the alkalies. This is a general property of the alkyl-ecgonines.
Consequently, according to the quantity of alkali used and to the duration of its eiiect the prevailing end product obtained will be at will either levomethyl-ecgonine corresponding to natural cocaine or its dextro rotary isomere (d. 1 methylecgonine) On its part, the alkali which has been added disappears gradually while saponifying a portion of the esters produced in the preceding stage of the alcoholysis. This disappearance of the free alkali may be rapid if the temperature is raised. The division in two parts practically ceases when the alkali has disappeared, although a very slow action is still apparent owing to autocatalysis of the divisible alkaloids when the same are still existent.
Oxides and alcoholates of alkali and alkaline earth metals, ammonia, certain amines and quaternary ammonium hydrates may be used as catalysts. Any alcohol capable of dissolving the catalyst may also be used as solvent of the alkaloids in the place of methylic alcohol.
The corresponding cocaines may be produced Without difiiculty by benzoylating according to the usual methods the ecgonine or pseudo-ecgonine esters.
I will now describe by way of example a mode of execution of the present process.
T0710 kgs. of amorphous coca alkaloids dissolved in 20 kgs. of methyl alcohol is added a concentrated caustic soda methyl alcohol solution in the proportion of 2 gr. of NaOH per kg. of alkaloids.
After three days contact at the ordinary room temperature (15 to 20 C.) the quantity of hydrochloric or sulfuric acid required for neutralizing the alkali is then added to the mixture and the methyl alcohol is completely distilled oil. Benzene is added to the residue and the solution is stirred with water acidulated with hydrochloric acid without any substantial excess in order to eliminate the basic products. There remains only aromatic esters in the benzene.
Ammonia is gradually added to the acid solution with agitation as long as a reaction takes place and a turbidity is present due to the separation of unattached amorphous alkaloids. Thereafter the unattached alkaloids thus separated are removed'by agitationwith benzene in 9 which they dissolve. Said alkaloids are separated from the solvent by distillation and may be treated in a new process. 1
The alkaline solution is then saturated with potassium carbonate which causes separation of the methylated ecgonine which is also recovered by stirring with benzene. The solvent is distilled ofi in vacuum.
The methylecgonine thus produced may be directly submitted to benzoylation or purified by conversion in hydrochloride.
When it is desired to produce a greater proportion of methylpseudoecgonine (d. I ecgonine) a greater proportion of alkali must be employed.
The mode of operation is the same as above described but at the end of the first three days of contact there will again be added 20 grs. of NaOH per kg. of alkaloids which are left to act during a week, at the end of that time the operation is begun to recover the methylpseudoecgonine into alkylated derivatives of ecgonine and dextro pseudo-ecgonine which consists in treating the alkaloids dissolved in an alcohol with small quantities of a compound having a strongly alkaline reaction, acting catalytically in homogeneous medium at room temperature and for a prolonged period to produce alcoholysis of said alkaloids and subsequent isomerization of the alkyl-ecgonine first produced. 7
2. A process for converting the alkaloids of coca into dextrorotary pseudo ecgonine esters, which comprises subjecting these alkaloids to alcoholysis, and subsequently catalytically forming the isomers of the alkyl-ecgonines first formed by contacting the same with an alkaline catalyst at room temperature and for a prolonged period.
solved in an alcohol in the presence of small quantities of a compound having a strongly basic reaction which acts as an alkaline catalyst and causes the alcoholysis of said alkaloids by simple digestion at room temperature and subsequently catalytically forming the isomers of the alkyl-eogonines first formed by continued contact for a prolonged time with the alkaline catalyst.
AUGUSTE TIRARD.
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US1925472A true US1925472A (en) | 1933-09-05 |
Family
ID=3425735
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US1925472D Expired - Lifetime US1925472A (en) | Processes for converting coca alka |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US1925472A (en) |
-
0
- US US1925472D patent/US1925472A/en not_active Expired - Lifetime
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